X-linked hypophosphatemia (XLH) is the most common heritable form of rickets/osteomalacia in the US.[unreadable] At all ages and irrespective of treatment there is a high incidence of hyperparathyroidism in XLH. Other[unreadable] manifestations include calcified entheses and arthritis. The explosion of new knowledge about phosphate[unreadable] metabolism makes this the right time for revisiting XLH both in terms of its pathogenesis and treatment. We[unreadable] hypothesize that elevated parathyroid hormone (PTH) levels make a signficiant contribution to the skeletal[unreadable] disease in XLH and propose to use paricalcitol, a non-hypercalcemic vitamin D analog, to suppress[unreadable] elevated PTH levels in this disease.[unreadable] In the first aim, we will perform a cross-sectional study to identify biomarkers of disease severity. We will[unreadable] develop a composite disease score in 70 patients with XLH using clinical parameters, radiographs, bone[unreadable] scintigraphy, and validated symptom questionnaires (WOMAC and SF-36). We will then assess the[unreadable] relationship of this composite score to the area under the curve (AUC) for circulating PTH, phosphate (P),[unreadable] and FGF23 levels, measured over a 24-hrs.[unreadable] In the second aim, we will conduct a 12-month randomized, double blind, placebo-controlled trial of[unreadable] paricalcitol in subjects with XLH and hyperparathyroidism. The dose will be titrated to achieve at least a 50%[unreadable] reduction in PTH levels. AUC for PTH during diurnal sampling performed at baseline and after 12 months[unreadable] of therapy will be the primary outcome measure with the dependent variables being the WOMAC/SF-36[unreadable] scores, and skeletal scintigrams at performed at baseline and post-treatment. We expect correction of[unreadable] hyperparathyroidism to be accompanied by symptomatic improvement and scintigraphic evidence for[unreadable] amelioration in skeletal disease . If successful, this trial will provide proof of concept for the use of[unreadable] paricalcitol in the treatment of XLH.[unreadable] This project will establish the clinical relevance of circulating PTH, FGF23 and phosphate as[unreadable] markers/mediators of disease in XLH and test the efficacy of non-hypercalcemic vitamin D analog therapy[unreadable] in XLH-associated hyperparathyroidism. The project will also serve as a basis for comparison with later[unreadable] (Phase 1) studies potentially directed at suppression of FGF23 action.